This proposal is designed to provide broad and thorough scientific training not available in traditional post-graduate research progrmas for physicians entering academic medicine. This proposal combines the scholarly excellence of graduate coursework and research at the Massachusetts Institute of Technology with the strengths of the superb clinical environment and basic medical research of the Massachusetts General Hospital. The sponsor, Dr. Herman N. Eisen, is an accomplished physician scientist who has had outstanding experience training young investigators. Two phases are envisioned, followed or perhaps split by a clinical fellowship in endocrinology. Phase I involves graduate level coursework in the departments of Biology, Chemistry and Mathematics at MIT. Research in Dr. Eisen's laboratory will center around the study of the antigen receptor of the T lymphocyte. The techniques being used in this laboratory to examine the receptor include serological approaches as well as recombinant DNA studies elucidating the structure of the Yield subunit. Learning to use a number of different tools and procedures from the fields of immunology and molecular genetics in one of the country's foremost laboratories will provide excellent training for future research with membrane receptors. More importantly, Dr. Eisen's sponsorship and laboratory, and the MIT academic offerings ensure a rigorous environment for the process of becoming a discerning competent scientist. Progress during Phase I will be evaluated by a committee of basic scientists with a commitment to medical education and the areas of research noted above. During Phase II, the approaches learned in Phase I will be applied to studying receptors of the endocrine system under both physiological and pathological conditions. An example of a possible Phase II project is the study of parathyroid hormone receptors on lymphocytes. The possible functions and regulation of these receptors raise many important issues of direct clinical relevance. A definite Phase II sponsor will be chosen in the future; such work would proceed under the general guidance of Drs. Henry Kronenberg, Gino Serge, and John Potts, all members of the Endocrine Unit at MGH